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1akj
From Proteopedia
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| - | [[Image:1akj.gif|left|200px]]<br /> | + | [[Image:1akj.gif|left|200px]]<br /><applet load="1akj" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1akj" size=" | + | |
caption="1akj, resolution 2.65Å" /> | caption="1akj, resolution 2.65Å" /> | ||
'''COMPLEX OF THE HUMAN MHC CLASS I GLYCOPROTEIN HLA-A2 AND THE T CELL CORECEPTOR CD8'''<br /> | '''COMPLEX OF THE HUMAN MHC CLASS I GLYCOPROTEIN HLA-A2 AND THE T CELL CORECEPTOR CD8'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The dimeric cell-surface glycoprotein CD8 is crucial to the positive | + | The dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of cytotoxic T cells in the thymus. The homodimer CD8alpha(alpha) or the heterodimer alpha beta stabilizes the interaction of the T-cell antigen receptor (TCR) with major histocompatibility complex (MHC) class I/peptide by binding to the class I molecule. Here we report the crystal structure at 2.7 A resolution of a complex between CD8alpha(alpha) and the human MHC molecule HLA-A2, which is associated with peptide. CD8alpha(alpha) binds one HLA-A2/peptide molecule, interfacing with the alpha2 and alpha3 domains of HLA-A2 and also contacting beta2-microglobulin. A flexible loop of the alpha3 domain (residues 223-229) is clamped between the complementarity-determining region (CDR)-like loops of the two CD8 subunits in the classic manner of an antibody-antigen interaction, precluding the binding of a second MHC molecule. The position of the alpha3 domain is different from that in uncomplexed HLA-A2, being most similar to that in the TCR/Tax/HLA-A2 complex, but no conformational change extends to the MHC/peptide surface presented for TCR recognition. Although these shifts in alpha3 may provide a synergistic modulation of affinity, the binding of CD8 to MHC is clearly consistent with an avidity-based contribution from CD8 to TCR-peptide-MHC interactions. |
==Disease== | ==Disease== | ||
| - | Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]], Ankylosing spondylitis, susceptibility to, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]], Hypoproteinemia, hypercatabolic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109700 109700]], Megakaryoblastic leukemia, acute OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606078 606078]], Stevens-Johnson syndrome, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]] | + | Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]], Ankylosing spondylitis, susceptibility to, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]], CD8 deficiency, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=186910 186910]], Hypoproteinemia, hypercatabolic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109700 109700]], Megakaryoblastic leukemia, acute OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606078 606078]], Stevens-Johnson syndrome, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]] |
==About this Structure== | ==About this Structure== | ||
| - | 1AKJ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus Human immunodeficiency virus]. Full crystallographic information is available from [http:// | + | 1AKJ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus Human immunodeficiency virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AKJ OCA]. |
==Reference== | ==Reference== | ||
| Line 18: | Line 17: | ||
[[Category: Human immunodeficiency virus]] | [[Category: Human immunodeficiency virus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Jones, E | + | [[Category: Jones, E Y.]] |
| - | [[Category: Stuart, D | + | [[Category: Stuart, D I.]] |
[[Category: Tormo, J.]] | [[Category: Tormo, J.]] | ||
[[Category: complex]] | [[Category: complex]] | ||
| Line 28: | Line 27: | ||
[[Category: t-cell]] | [[Category: t-cell]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:45:29 2008'' |
Revision as of 09:45, 21 February 2008
|
COMPLEX OF THE HUMAN MHC CLASS I GLYCOPROTEIN HLA-A2 AND THE T CELL CORECEPTOR CD8
Contents |
Overview
The dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of cytotoxic T cells in the thymus. The homodimer CD8alpha(alpha) or the heterodimer alpha beta stabilizes the interaction of the T-cell antigen receptor (TCR) with major histocompatibility complex (MHC) class I/peptide by binding to the class I molecule. Here we report the crystal structure at 2.7 A resolution of a complex between CD8alpha(alpha) and the human MHC molecule HLA-A2, which is associated with peptide. CD8alpha(alpha) binds one HLA-A2/peptide molecule, interfacing with the alpha2 and alpha3 domains of HLA-A2 and also contacting beta2-microglobulin. A flexible loop of the alpha3 domain (residues 223-229) is clamped between the complementarity-determining region (CDR)-like loops of the two CD8 subunits in the classic manner of an antibody-antigen interaction, precluding the binding of a second MHC molecule. The position of the alpha3 domain is different from that in uncomplexed HLA-A2, being most similar to that in the TCR/Tax/HLA-A2 complex, but no conformational change extends to the MHC/peptide surface presented for TCR recognition. Although these shifts in alpha3 may provide a synergistic modulation of affinity, the binding of CD8 to MHC is clearly consistent with an avidity-based contribution from CD8 to TCR-peptide-MHC interactions.
Disease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142800], Ankylosing spondylitis, susceptibility to, 1 OMIM:[142800], CD8 deficiency, familial OMIM:[186910], Hypoproteinemia, hypercatabolic OMIM:[109700], Megakaryoblastic leukemia, acute OMIM:[606078], Stevens-Johnson syndrome, susceptibility to OMIM:[142800]
About this Structure
1AKJ is a Protein complex structure of sequences from Homo sapiens and Human immunodeficiency virus. Full crystallographic information is available from OCA.
Reference
Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2., Gao GF, Tormo J, Gerth UC, Wyer JR, McMichael AJ, Stuart DI, Bell JI, Jones EY, Jakobsen BK, Nature. 1997 Jun 5;387(6633):630-4. PMID:9177355
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